There is no tool more essential to cancer research than the experimental tumor. Every therapeutic and preventative strategy employs such tumors, and tumors growing in animals are instrumental to basic studies of cancer biology. Many experimental tumors are injected subcutaneously because subsequent growth can be followed visually. However, it is often preferable to have tumors grow internally. Such internal growths more closely mimic the environment of naturally occurring tumors, because host factors (blood supply, immune recognition and destruction, extracellular matrix, etc.) are far different at internal sites than in the skin. Metastasis, a defining feature of malignancy, cannot be assessed through observation of the skin. Moreover, the size of subcutaneous tumors often does not reflect the true tumor load, as the volume composed of stroma, necrosis, and scar tissue cannot be distinguished from that occupied by neoplastic cells.
For these reasons, internal tumors have also been widely used for studies of tumor biology. However, the presence of internal tumors is generally apparent only when symptoms develop, which generally occurs quite late during tumorigenesis. Surgical approaches to detect smaller internal tumors can be useful, but anesthetics and surgical manipulation can disturb the natural course of tumorigenesis and introduce other variables into the analysis. Human lactic dehydrogenase and α-1-antitrypsin have been proposed as serum markers in xenograft-nude mice tumor models. However, the repetitive anesthesia and blood collections required for these approaches have hampered their widespread use.
In addition, mice with internal tumors are generally sacrificed at the end of an experimental protocol to determine how the tumors have responded. Only a single time point can be assessed using this approach, and multiple mice must be studied to minimize the effects of tumor and host heterogeneity. Imaging techniques provide a way of following tumor growth in situ, but are only applicable to rather large tumors.
To overcome the problems noted above, there is a need in the art for a system for monitoring internal tumor growth that would (i) provide a quantitative measure of neoplastic cell content, (ii) be cost-effective and simple to implement, and (iii) be broadly applicable to diverse tumor types and hosts.